Polymorphisms and diazinon and malathion levels in the etiology of breast cancer: a case-control study in Mazandaran Province, North of Iran.

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Bibliographic Details
Title:	Polymorphisms and diazinon and malathion levels in the etiology of breast cancer: a case-control study in Mazandaran Province, North of Iran.
Alternate Title:	Polimorfismos y niveles de diazinón y malatión en la etiología del cáncer de mama: un estudio de casos y controles en la provincia de Mazandaran, al norte de Irán.
Authors:	Golmohammadzadeh, Golpar¹, Mohammadpour, Abbas², Ahangar, Nematollah³, Shokrzadeh, Mohammad³
Source:	Revista Latinoamericana de Hipertensión. 2019, Vol. 14 Issue 5, p525-536. 12p.
Subjects:	BREAST cancer, ETIOLOGY of cancer, MALATHION, ORGANOPHOSPHORUS pesticides, BRCA genes, GLUTATHIONE transferase, FENITROTHION
Geographic Terms:	MAZANDARAN (Iran), IRAN
Abstract:	Breast cancer is the first leading cause of cancer-related death in women. Xenobiotic-Metabolizing Enzymes (XMEs) contribute to the detoxification of numerous cancer therapy-induced products. In the metabolism of xenobiotics, cytochrome P450s or monooxygenases and Glutathione –s transferase (GSTs) perform an important function by catalyzing the hydroxylation reaction and conjugation of glutathione (GSH) to a wide variety of xenobiotics. Pesticides, which are excessively used in northern Iran, are one of the most-important risk factors for breast cancer incidence. They detoxify by phase I and II enzymes. The aim of this study was to evaluate the association of CYP1A1 (rs4646421), CYP1B1 (rs1056836), CYP2C8 (rs1058930), CYP19A1 (rs749292) and GSTP1 (rs 1695) polymorphisms and serum levels of pesticides (Diazinon and Malathion) with the risk of breast cancer in Mazandaran province. This cross-sectional case-control study included 72 patients and 51 healthy individuals who were recruited. It was performed between October 2017 to May 2018 in Oncology department at Imam Hospital in Sari City. Breast cancer patients with known clinicopathological characters and healthy women, as control, were genotyped for genes polymorphisms by PCR-RFLP and GC-MS method used for quantification of poisons. Chisquare test, Fisher exact test, and logistic regression model were applied for statistical analysis. The results of the experiments showed that there were significant relationships between two groups and the age of the patients was significantly higher than the control group (p = 0.044). Regarding the relationship between the genotypes of each gene and breast cancer risk, using a logistic regression model in two normalized and age-adjusted models, it was determined that in CYP2C8 genotype, those having the CG allele, increased the risk of breast cancer in adjusted model (CI=95%1.11,75.84). In the CYP19A1 gene of individuals with GA genotype, the risk of breast cancer increased in non-adjusted model (CI95%=1/52-27/21) about the CYP1B1 gene, people with two genotypes of CG + GG were associated with a higher risk of breast in non-adjusted and adjusted model (CI71/5 – 19/1 95% =) (CI=95% 1.31,6.57). In CYP2C8 gene, the G allele had a protective effect on breast cancer and decreased the risk of breast cancer (P = 0.02) and in GSTP1 gene, the Gallele increased the risk of breast cancer (P=0.0480). Moreover, in CYP1B1 gene, G allele decreased the risk of breast cancer (P=0.0271). Regarding the serum levels of OPs, Diazinon in the case group had a much lower level than the control group but (p<0.001) there was a significant relationship between serum levels of Diazinon and risk of breast cancer (p<0.001). The results of the current study confirmed the association between CYP2C8 (rs1058930), CYP19A1 (rs749292) and CYP1B1 (rs1056836) gene polymorphisms and increased the risk of breast cancer. Also, there was a significant relationship between serum levels of Diazinon and risk of breast cancer in women in Mazandaran province [ABSTRACT FROM AUTHOR]
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Database:	MedicLatina

Description
Abstract:	Breast cancer is the first leading cause of cancer-related death in women. Xenobiotic-Metabolizing Enzymes (XMEs) contribute to the detoxification of numerous cancer therapy-induced products. In the metabolism of xenobiotics, cytochrome P450s or monooxygenases and Glutathione –s transferase (GSTs) perform an important function by catalyzing the hydroxylation reaction and conjugation of glutathione (GSH) to a wide variety of xenobiotics. Pesticides, which are excessively used in northern Iran, are one of the most-important risk factors for breast cancer incidence. They detoxify by phase I and II enzymes. The aim of this study was to evaluate the association of CYP1A1 (rs4646421), CYP1B1 (rs1056836), CYP2C8 (rs1058930), CYP19A1 (rs749292) and GSTP1 (rs 1695) polymorphisms and serum levels of pesticides (Diazinon and Malathion) with the risk of breast cancer in Mazandaran province. This cross-sectional case-control study included 72 patients and 51 healthy individuals who were recruited. It was performed between October 2017 to May 2018 in Oncology department at Imam Hospital in Sari City. Breast cancer patients with known clinicopathological characters and healthy women, as control, were genotyped for genes polymorphisms by PCR-RFLP and GC-MS method used for quantification of poisons. Chisquare test, Fisher exact test, and logistic regression model were applied for statistical analysis. The results of the experiments showed that there were significant relationships between two groups and the age of the patients was significantly higher than the control group (p = 0.044). Regarding the relationship between the genotypes of each gene and breast cancer risk, using a logistic regression model in two normalized and age-adjusted models, it was determined that in CYP2C8 genotype, those having the CG allele, increased the risk of breast cancer in adjusted model (CI=95%1.11,75.84). In the CYP19A1 gene of individuals with GA genotype, the risk of breast cancer increased in non-adjusted model (CI95%=1/52-27/21) about the CYP1B1 gene, people with two genotypes of CG + GG were associated with a higher risk of breast in non-adjusted and adjusted model (CI71/5 – 19/1 95% =) (CI=95% 1.31,6.57). In CYP2C8 gene, the G allele had a protective effect on breast cancer and decreased the risk of breast cancer (P = 0.02) and in GSTP1 gene, the Gallele increased the risk of breast cancer (P=0.0480). Moreover, in CYP1B1 gene, G allele decreased the risk of breast cancer (P=0.0271). Regarding the serum levels of OPs, Diazinon in the case group had a much lower level than the control group but (p<0.001) there was a significant relationship between serum levels of Diazinon and risk of breast cancer (p<0.001). The results of the current study confirmed the association between CYP2C8 (rs1058930), CYP19A1 (rs749292) and CYP1B1 (rs1056836) gene polymorphisms and increased the risk of breast cancer. Also, there was a significant relationship between serum levels of Diazinon and risk of breast cancer in women in Mazandaran province [ABSTRACT FROM AUTHOR]
ISSN:	18564550